{
  "abstract": "Objectives To identify genetic variants in the NADPH oxidase 2 (NOX2) complex associated with systemic lupus erythematosus (SLE), secondary antiphospholipid syndrome (sAPS), or Sjögren’s disease (SjD) in a Scandinavian cohort, and to assess potential additive effects of such variants on disease association and age at diagnosis.Methods Targeted DNA sequencing and pyrosequencing were used to analyze genetic variants in genes encoding components of the NOX2 complex in 1,645 Scandinavian patients with SLE, sAPS or SjD, and 1,025 healthy controls. In total, 276 genetic variants were analyzed for SLE and sAPS, and 310 for SjD and controls. Variant frequencies were compared between disease groups and controls, and combinations of variants were evaluated for additive effects. Median age at diagnosis was compared between genotypes in SLE to explore potential associations with disease onset.Results Among the 310 genetic variants analyzed, two known missense variants, NCF1-339 and NCF2-389, were associated with SLE, sAPS and SjD. No novel variants with disease association were identified. When combined, NCF1-339 and NCF2-389 showed additive effects, with higher odds of carrying both variants in patients with SLE ( figure 1 A), and to a lesser extent in those with SjD (figure 1 B) and sAPS (figure 1 C), compared with healthy controls. Furthermore, SLE patients carrying both variants were diagnosed at a younger age than those without these variants (figure 1 D).Abstract PO:06:174 Figure 1Additive effects of risk variants in the NOX2 complex. (A-B) The odds of carrying the NCF1-339 and NCF2-389 risk variants are increased compared to healthy controls for (A) SLE and (B) SiD. The odds ratio (OR) for carrying the risk variants NCF1-T NCF2-GT in SLE were 8.9 (CI 95% 3.0 to 26.1) and in SiD were 3.8 (CI 95% 1.2 to 11.6). (C) Among SLE patients, the odds of carrying these risk variants compared between those with sAPS and those without were 2.9 (CI 95% 0.98 to 7.8). (D) SLE patients carrying the risk variants were, on average, diagnosed at a younger age compared to non-carriers. The median age for SLE patients carrying the risk variants NCF1-T NCF2-GT were 25 (CI 95% 14 to 36) compared to the normal variant NCF1-C NCF2-GG 34 (CI 95% 32 to 36)Conclusions No novel genetic variants in the NOX2 complex were associated with SLE, sAPS, or SjD. However, the known missense variants NCF1-339 and NCF2-389 showed additive effects, being associated with increased odds of SLE and SjD and with an earlier age at diagnosis in SLE. In sAPS, a non-significant trend suggested a possible association. These findings support a combined genetic contribution within the NOX2 complex to autoimmune disease susceptibility.",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Andreas Jern"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Christian Lundtoft"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Birgitta Gullstrand"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Johanna Sandling"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Elisabeth Svenungsson"
    },
    {
      "affiliations": [
        "Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden"
      ],
      "name": "Christopher Sjöwall"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Andreas Jönsen"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Petrus Linge"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Robin Kahn"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Gunnel Nordmark"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Bergen, Norway"
      ],
      "name": "Marie Wahren-Herlenius"
    },
    {
      "affiliations": [
        "Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Rikard Holmdahl"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Lars Rönnblom"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences Lund, Rheumatology, Lund University, and Skåne University Hospital, Lund, Sweden"
      ],
      "name": "Anders Bengtsson"
    }
  ],
  "title": "PO:06:174 Additive effects of genetic variants in NADPH oxidase 2 complex in systemic lupus erythematosus, secondary antiphospholipid syndrome and Sjögren’s disease",
  "uid": "17f73a49-bce0-5847-b6a4-1683d4b0b1ac"
}